Sugar Overconsumption during Adolescence Selectively Alters Motivation and Reward Function in Adult Rats

International audienceBACKGROUND:There has been a dramatic escalation in sugar intake in the last few decades, most strikingly observed in the adolescent population. Sugar overconsumption has been associated with several adverse health consequences, including obesity and diabetes. Very little is known, however, about the impact of sugar overconsumption on mental health in general, and on reward-related behavioral disorders in particular. This study examined in rats the effects of unlimited access to sucrose during adolescence on the motivation for natural and pharmacological rewards in adulthood.METHODOLOGY/PRINCIPAL FINDINGS:Adolescent rats had free access to 5% sucrose or water from postnatal day 30 to 46. The control group had access to water only. In adulthood, rats were tested for self-administration of saccharin (sweet), maltodextrin (non-sweet), and cocaine (a potent drug of abuse) using fixed- and progressive-ratio schedules, and a concentration-response curve for each substance. Adult rats, exposed or not exposed to sucrose, were tested for saccharin self-administration later in life to verify the specificity of adolescence for the sugar effects. Sugar overconsumption during adolescence, but not during adulthood, reduced the subsequent motivation for saccharin and maltodextrin, but not cocaine. This selective decrease in motivation is more likely due to changes in brain reward processing than changes in gustatory perception.CONCLUSIONS/SIGNIFICANCE:Sugar overconsumption induces a developmental stage-specific chronic depression in reward processing that may contribute to an increase in the vulnerability to reward-related psychiatric disorders

Caractérisation des aspects consommatoires, motivationnels et anticipatoires du comportement alimentaire (implication de la dopamine et des opioïdes endogènes)

La prise de nourriture est un comportement étroitement régulé par des systèmes homéostatiques et hédoniques. Il présente des aspects motivationnels, consommatoires et anticipatoires dont la modulation est assurée par des neurotransmetteurs tels que les opioides et la dopamine. Notre étude vise à caractériser les composantes motivationnelles, anticipatoires et consommatoires en fonction de la palatabilité des aliments et de l'état homéostatique des animaux, et étudier l'implication des systèmes opioidergique et dopaminergique dans le contrôle de ces aspects. Les résultats obtenus renforcent l'idée que le système opioide régule la prise de nourriture en modulant la perception des propriétés hédoniques des aliments. La dopamine semble être plus impliquée dans la régulation de l'activité anticipatoire lorsque les stimuli sont très pertinents pour les organismes. Ainsi, elle permettrait d'évaluer le rapport effort/bénéfice des actions à exécuter.Feeding behavior is highly regulated by homeostatic and hedonic systems The motivational, consummatory and anticipatory components of this behavior appear to be differentially regulated by opioids and dopamine. Our study is aimed first to characterize the motivational, anticipatory and consummatory components of feeding taking into account food palatability and homeostatic state of the animals ; and second, to study the implication of the opioid and dopaminergic systems on the control of these different components. Our results reinforce the idea that the opioid system regulates feeding through the modulation of food palatability perception. The dopaminergic system seems to be more implicated in the regulation of the anticipatory activity related to very relevant stimuli. Also, it may allow the evaluation of the cost/benefits to perform a given action.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

The Effects of response operandum and prior food training on intravenous nicotine self-administration in rats

Rationale: Nicotine intravenous self-administration (IVSA) in rats has been conducted using a variety of methodological procedures with equally variable results. Objectives: Here, we addressed the importance of the type of response operandum and prior instrumental training with a natural reinforcer on nicotine IVSA and reinstatement. Methods: Rats were tested for spontaneous acquisition of IVSA using either nose poke (NP) or lever press (LVR) operandum. A dose-response test was then conducted, followed by extinction and cue- and nicotine-induced reinstatement. Results: The use of the NP operandum resulted in markedly higher levels of IVSA across acquisition and across dose-response testing compared with the LVR group. Whereas both groups reinstated following a nicotine prime, only the LVR group demonstrated cue-induced reinstatement. As a positive control, the experiment was repeated with cocaine as the reinforcer: equivalent levels of IVSA were observed across all tests, irrespective of operandum. When rats self-administering nicotine received instrumental training with a sucrose reinforcer prior to IVSA, a facilitated acquisition of IVSA was observed in both LVR and NP groups to a similar extent (the effect of operandum remained), but had little effect on responding thereafter. During reinstatement testing, both groups now displayed cue- and nicotine-induced reinstatement, but this was also evident in saline control animals that had never received nicotine. Conclusions: These results suggest that, unlike cocaine, an increased physical response requirement can decrease nicotine intake. It also indicates that operandum and prior sucrose training may influence the role that visual cues play in nicotine dependence.12 page(s

Repeated Episodes of Heroin Cause Enduring Alterations of Circadian Activity in Protracted Abstinence

Opiate withdrawal is followed by a protracted abstinence syndrome consisting of craving and physiological changes. However, few studies have been dedicated to both the characterization and understanding of these long-term alterations in post-dependent subjects. The aim of the present study was to develop an opiate dependence model, which induces long-lasting behavioral changes in abstinent rats. Here, we first compared the effects of several protocols for the induction of opiate dependence (morphine pellets, repeated morphine or heroin injections) on the subsequent response to heroin challenges (0.25 mg/kg) at different time points during abstinence (3, 6, 9 and 18 weeks). In a second set of experiments, rats were exposed to increasing doses of heroin and subsequently monitored for general circadian activity up to 20 weeks of abstinence. Results show that heroin injections rather than the other methods of opiate administration have long-term consequences on rats’ sensitivity to heroin with its psychostimulant effects persisting up to 18 weeks of abstinence. Moreover, intermittent episodes of heroin dependence rather than a single exposure produce enduring alteration of the basal circadian activity both upon heroin cessation and protracted abstinence. Altogether, these findings suggest that the induction of heroin dependence through intermittent increasing heroin injections is the optimal method to model long-term behavioral alterations during protracted abstinence in rats. This animal model would be useful in further characterizing long-lasting changes in post-dependent subjects to help understand the prolonged vulnerability to relapse

Repeated Episodes of Heroin Cause Enduring Alterations of Circadian Activity in Protracted Abstinence

Opiate withdrawal is followed by a protracted abstinence syndrome consisting of craving and physiological changes. However, few studies have been dedicated to both the characterization and understanding of these long-term alterations in post-dependent subjects. The aim of the present study was to develop an opiate dependence model, which induces long-lasting behavioral changes in abstinent rats. Here, we first compared the effects of several protocols for the induction of opiate dependence (morphine pellets, repeated morphine or heroin injections) on the subsequent response to heroin challenges (0.25 mg/kg) at different time points during abstinence (3, 6, 9 and 18 weeks). In a second set of experiments, rats were exposed to increasing doses of heroin and subsequently monitored for general circadian activity up to 20 weeks of abstinence. Results show that heroin injections rather than the other methods of opiate administration have long-term consequences on rats’ sensitivity to heroin with its psychostimulant effects persisting up to 18 weeks of abstinence. Moreover, intermittent episodes of heroin dependence rather than a single exposure produce enduring alteration of the basal circadian activity both upon heroin cessation and protracted abstinence. Altogether, these findings suggest that the induction of heroin dependence through intermittent increasing heroin injections is the optimal method to model long-term behavioral alterations during protracted abstinence in rats. This animal model would be useful in further characterizing long-lasting changes in post-dependent subjects to help understand the prolonged vulnerability to relapse

The Addition of five minor tobacco alkaloids increases nicotine-induced hyperactivity, sensitization and intravenous self-administration in rats

Several minor tobacco alkaloids have been found to exhibit properties pharmacologically relevant to the addictive profile of tobacco; however, little is known of their effects on a behavioural model of drug addiction. In this study we compared the locomotor and reinforcing effects of intravenous nicotine (30 μg/kg per infusion) vs. a cocktail of nicotine plus five minor alkaloids found in tobacco smoke (anabasine, nornicotine, anatabine, cotinine and myosmine). Rats were initially tested for their locomotor response to nicotine or nicotine plus the minor alkaloids with six intravenous injections over 1 h. We then assessed the spontaneous acquisition of intravenous self-administration with nicotine or nicotine plus the minor alkaloids, under a fixed-ratio 1 schedule followed by responding on a fixed-ratio 5 schedule, progressive-ratio schedule and a single within-session ascending dose–response test. The activity test was repeated following the progressive-ratio phase to assess locomotor sensitization. A second group of rats were then tested on the locomotor procedure to better clarify the role of each individual minor alkaloid in nicotine-induced locomotor activity. Compared to nicotine alone, addition of the minor tobacco alkaloids increased locomotor activity and increased locomotor sensitization following self-administration. During fixed-ratio 5, progressive ratio and the dose–response test, rats receiving nicotine plus the minor alkaloids responded significantly more than those receiving nicotine alone. Testing of each minor alkaloid in the second experiment indicated that anatabine, cotinine and myosmine individually increased nicotine-induced locomotor activity. These results suggest that the minor tobacco alkaloids, particularly anatabine, cotinine and myosmine, may increase the motivation for nicotine and thus facilitate smoking behaviour.12 page(s

Nicotine-induced locomotor activity is increased by preexposure of rats to prenatal stress

International audienceGenetic factors are believed to play a predominant role in the individual differences observed in behavioral and pharmacological responses to drugs of abuse. An increasing literature indicates, however, that epigenetic factors can be involved as well. In this report we examined whether developmental changes induced by prenatal stress could alter the way animals respond to the psychostimulant effect of nicotine when adults. The results show that nicotine induces a dose-dependent increase of locomotor activity in both groups, and that prenatally-stressed animals exhibit a higher behavioral response at all doses. This study emphasizes the importance of early environment in the later development of drug-related behavior

Different populations of subthalamic neurons encode cocaine vs. sucrose reward and predict future error

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Long-lasting deficits in hedonic and nucleus accumbens reactivity to sweet rewards by sugar overconsumption during adolescence

Adolescence is a critical period characterized by major neurobiological changes. Chronic stimulation of the reward system might constitute an important factor in vulnerability to pathological development. In spite of the dramatic increase in the consumption of sweet palatable foods during adolescence in our modern societies, the long-term consequences of such exposure on brain reward processing remain poorly understood. Here, we investigated in rats the long-lasting effects of sugar overconsumption during their adolescence on their adult reactivity to the hedonic properties of sweet rewards. Adolescent rats with continuous access to 5% sucrose solution (from postnatal day 30-46) showed escalating intake. At adulthood (post-natal day 70), using two-bottle free choice tests, sucrose-exposed rats showed lower intake than non-exposed rats suggesting decreased sensitivity to the rewarding properties of sucrose. In Experiment 1, we tested their hedonic-related orofacial reactions to intraoral infusion of tasty solutions. We showed that sucrose-exposed rats presented less hedonic reactions in response to sweet tastes leaving the reactivity to water or quinine unaltered. Hence, in Experiment 2, we observed that this hedonic deficit is associated with lower c-Fos expression levels in the nucleus accumbens, a brain region known to play a central role in hedonic processing. These findings demonstrate that a history of high sucrose intake during the critical period of adolescence induces long-lasting deficits in hedonic treatment that may contribute to reward-related disorders